Gastrin (G) stimulates gastric HC1 secretion, but the mechanism of action is unknown. We have established a quantitative cytochemical assay for oxyntic cell carbonic anhydrase (CA) in 18mu sections of guinea pig gastaric tissue in which the reaction can be specifically localized to oxyntic cells. The assay is unique for its sensitivity to G (10-16M). Potentiating actions between G and histamine (H) were found. Both dose- and time-dependent disensitization occurred. G was found to have Ca++- dependent and H-mediated actions. These studies suggest that there are several modes of G activation of oxyntic cells in which H1 and H2 components of H, Ca++, cAMP and prostaglandins may be important. Potentiating and desensitizing actions may be not only dose-related but dependent upon changes in the time course of action. We propose to examine: the roll of H1 and H2 components of H in G acton; the interaction of G with structurally related peptides; the effect of stimulators and inhibitors of acid secretion on efficacy and potency of G; time course of interactions of combinations of agonists; effects of perturbations of Ca++ flux with Ca++ ionophore and Ca++ antagonists; the role of exogenous db-cAMP and incresing endogenous cAMP; the role of exogenous prostaglandins and inhibition of their synthesis; the relation between cellular metabolism and respiration and activation of CA using inhibitors of protein synthesis and respiration; and the site of G action using antisera to oxyntic cells, G and the Various isoenzymes of Ca in gastric tissue. These studies should provide new information on the ode of actio of G and interaction with other secretogogues in the stimulus-excitation coupling of oxyntic cell function. These studies are aimed at improving our understanding of the control of acid secretion upon which a sound therapeutic approach to peptic ulcer disease can be based.